Organotypic cultures of central and/or peripheral neural tissues will be used in conjunction with muscle explants as model systems for studies in cellular neurobiology. The unique geometry of these relatively two-dimensional cellular arrays in vitro will be exploited to facilitate close correlation of the bioelectric and cytologic properties of cultured neurons and muscle cells under various experimental conditions, including systematic application of patterned electric stimuli as well as pharmacologic, immunologic and other selective physico-chemical agents. Since neural tissues from embryonic or neonatal mammals adapt well to culture conditions, emphasis will be placed on physiologic studies during diffentiation and development of these isolated groups of neurons and related cells. Our cultures will include specific neuronal networks in explants of fetal mouse spinal cord, medulla, hippocampus and cerebral neocortex. Histologic studies, including electron microscopy and cytochemical techniques will be utilized to analyze the structural basis of the functional synaptic networks which form at critical stages of maturation in vitro. These model systems will permit more direct analyses of inductive, trophic or other chemical factors which underly synaptogenesis and formation of organized cell assemblies, with patterned neuronal circuit connections. BIBLIOGRAPHIC REFERENCES: Crain, S.M. (1976) Neurophysiologic Studies in Tissue Culture, Raven Press, N.Y., 300 pp. (in press). Crain, S.M. (1976) Development of specific sensory-evoked synaptic networks in CNS tissue cultures. In: Electrobiology of Nerve, Synapse, and Muscle (Grundfest Festschrift). Ed. by J.P. Reuben, D.P. Purpura, M.V.L. Bennett and E.R. Kandel, Raven Press, N.Y. (in press).